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Frequent Novel Variations Within Msh2 and Mlh1 Genes in a Subset of Iranian Families With Hereditary Non-Polyposis Colorectal Cancer Publisher



Javan S1 ; Andalib A1 ; Bereshneh AH2 ; Emami MH3 ; Salehi R4 ; Karami F5
Authors
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Authors Affiliations
  1. 1. Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  2. 2. Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Internal Medicine, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  4. 4. Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  5. 5. Department of Medical Genetics, Applied Biophotonics Research Center, Sciences and Research Branch, Islamic Azad University, Tehran, Iran

Source: Acta Medica Iranica Published:2019


Abstract

Hereditary non-polyposis colorectal cancer (HNPCC) is the most frequent autosomal dominant predisposition for development of colorectal cancer (CRC) caused by germline defects in mismatch repair (MMR) genes. Current study was aimed to find genetic variations in MSH2 and MLH1 genes and their correlation with the serum levels of Carcinoembryonic Antigen (CEA) in seven Iranian HNPCC families. Seven unrelated Iranian families including 11 HNPCC patients and 7 affected family members were selected. They were initially screened for mutations in exons 7 of MSH2 and exon 15 of MLH1 gene through polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP). Positive PCR results were further analyzed through exon sequencing. Serum CEA level was determined using the ELISA test. PCR-SSCP was positive in 8 out of 18 patients (44%) for exons 7 of MSH2 gene, whereas two samples (11%) demonstrated to bear a mutation in exon 15 of the MLH1 gene. Sequencing analysis of both amplified exons in positive and negative samples have confirmed no mutation in negative samples while revealed 5 and 7 novel mutations in exons 7 and 15, respectively. The mean serum concentration of CEA had a significant difference between HNPCC patients and their healthy family members. Our results demonstrated that the PCR-SSCP method has high specificity and sensitivity in the first step of mutation screening of HNPCC families. High frequency of novel alterations found in the current assay may revise the mutation screening of MSH2 and MLH1 genes and abet further assessment of their frequency among individual HNPCC patients. © 2019 Tehran University of Medical Sciences. All rights reserved.